The present invention relates generally to the removal of ectoparasites from the bodies of humans and animals, and more particularly to a topical treatment to facilitate such removal.
Ectoparasite infestation of humans and animals is a serious health problem throughout the world. Of particular importance as a public health issue is pediculosis, or infestations with lice, which are pervasive among children and can quickly be spread in a school setting. A very common parasite is Pediculus humanus var capitis, the common head louse, although there are other important parasites, including Pthirus pubis (the pubic louse) and Pediculus humanus var corporis (the body louse). Infestations are frequently accompanied by itching and skin damage. Infections and other adverse conditions may occur when the skin is scratched in an attempt to relieve the itching. Further, lice are known to be capable of transmitting serious diseases, including trench fever, relapsing fever and typhus.
Pediculosis is most frequently treated by applying pesticidal compositions, such as lotions or shampoos, to the affected body areas, such as the hair, and then exhaustively combing with a fine-tooth comb made especially for the purpose of removing nits. Commercially available preparations may include as their active ingredients pyrethrins, piperonyl butoxide, malathion, lindane or permethrins, many of which unfortunately have neurotoxic properties, are readily absorbed through the skin and therefore can establish undesirable systemic concentrations. It is perceived that the effectiveness of pesticides has recently diminished, as the parasites appear to continually become more resistant to their action. The resistance may be aggravated by small amounts of residual pesticide on the treated areas, following the procedure. This resistance also contributes to an increased opportunity for toxic systemic exposure to the active ingredients, since the preparations must be applied repeatedly to obtain an eradication of the infestation. Further, the pesticides do not usually kill the parasite""s eggs that may be present on a host, so the tedious mechanical removal techniques must also be used.
Successful ectoparasite infestation treatment involves not only removal of pests from the host, but also a concurrent removal of the pests from the environment. It is necessary to scrupulously clean clothing, bed linens, etc. to avoid reinfestation. Of course, if other residents of the household are hosting ectoparasites, the probability of eradicating them on an individual is quite low.
DiNapoli et al., xe2x80x9cEradication of Head Lice with a Single Treatment,xe2x80x9d American Journal of Public Health, Vol. 78, pages 978-980, 1988, reported a study in which 7 percent of patients treated with a commercial 1 percent permethrin cream rinse, and 16 percent of patients treated with a commercial product containing 0.3 percent pyrethrins, 3 percent piperonyl butoxide, 1.2 percent petroleum distillate and 2.4 percent benzyl alcohol, experienced adverse reactions including pruritis, erythema, tingling, rash and other conditions. Further, by 14 days following treatment 38 percent of the patients treated with the pyrethrin product were found to host live lice, considered a treatment failure. Permethrin is described as having residual activity on the hair for up to two weeks.
R. J. Roberts et al., xe2x80x9cComparison of Wet Combing with Malathion for Treatment of Head Lice in the UK: a Pragmatic Randomised Controlled Trial,xe2x80x9d The Lancet, Vol. 356, pages 540-544, 2000, report that mechanical removal of lice with a commercial comb every 3-4 days for two weeks gave a xe2x80x9ccurexe2x80x9d rate of only 38 percent, while two treatments with 0.5 percent malathion lotion seven days apart gave a xe2x80x9ccurexe2x80x9d rate of 78 percent.
Published results for the various topical pesticidal treatments were compared by. R. H. Vander Stichele et al., xe2x80x9cSystematic Review of Clinical Efficacy of Topical Treatments for Head Lice,xe2x80x9d British Medical Journal, Vol. 311, pages 604-608, 1995. It was concluded that only permethrin had sufficient evidence of efficacy.
There are other approaches to treating the infestations, including the application of heavy, oily substances such as mineral oil, petrolatum, mayonnaise and the like in an attempt to suffocate the ectoparasites, but these have not been found particularly effective, esthetically pleasing or convenient. One major disadvantage of such treatments is the prolonged time (usually several hours) required to achieve suffocation, after the agent has been applied.
The suffocation technique has been refined, such as by the approach of U.S. Pat. No. 6,139,859 to Precopio which utilizes air-impermeable water-dispersible liquid compositions containing surface active agents. Another type of treatment refinement is the technique of Pearlman et al. in PCT International Publication WO 99/18800, involving the topical application of surfactant substances as xe2x80x9cpediculostatic agentsxe2x80x9d which immobilize the parasites to permit their removal by combing.
Various cosmetic products that generate heat in the presence of moisture have been reported. U.S. Pat. No. 3,250,680 to Menkart et al. describes cleaning and other liquid, creamy or pasty consumer product compositions that contain the alkali metal aluminosilicate called Molecular Sieve 5A; when applied following contact with water, the compositions are said to impart a pleasing warmth to the skin. U.S. Pat. No. 4,379,143 to Sherry et al. is directed toward analgesic balms, ointments or lotions that contain activated zeolites which hydrate exothermically using skin moisture and can thus provide heat to relieve muscle pain and the like.
The application of very hot water can kill head lice on articles such as combs and brushes. However, the temperatures and times required for efficacy would not be tolerable on the skin of a person or animal.
It remains desirable to have a treatment for ectoparasitic infestations which is efficacious, acts rapidly and does not generate great discomfort or require any exposure of the host to toxic agents.
The present invention is a treatment for ectoparasitic infestations, particularly those involving fleas, ticks, mites or lice, comprising establishing temperature conditions above or below the normal range of skin temperatures in the infested area, for a time sufficient to immobilize or kill the ectoparasites, then removing the pests by mechanical means such as combing.
In one embodiment, the invention involves compositions which generate elevated temperatures when contacted with water, such as is present in moistened hair or skin. The elevated temperatures are maintained for a time sufficient to cause immobilization and/or mortality of the parasites, facilitating their mechanical removal by combing and other techniques.
Treatment can be conducted using a composition which generates heat, when contacted with water. In one embodiment, the composition is a particulate solid, a semi-solid or a fluid containing substantially no aqueous matter, or in some instances only a small amount of water, and which contains a particulate inorganic substance that can react exothermally with water. Examples of suitable substances are aluminosilicates and alkaline earth metal oxides. The exothermic reaction is not necessarily one which results in formation of any new chemical compound, but can be an absorption-type reaction.
In another embodiment, the temperature is reduced below the usual range of skin temperatures for the infested area.
The invention will be described primarily as it relates to the reduction of human head lice infestations, although those skilled in the art will recognize its applicability to other ectoparasites and animal subjects, and the inventors intend that their invention will have such applicability.
In the following description and the claims, it is intended that a reference to a percentage means percent by weight, unless the context clearly indicates otherwise. Since the chemical names for certain composition ingredients are quite cumbersome, some ingredients are identified herein by their adopted names as given in standard reference works, including J. A. Wenninger et al, Eds., International Cosmetic Ingredient Dictionary and Handbook, 8th Ed., The Cosmetic, Toiletry and Fragrance Association, Washington, D.C., 1999.
The present invention extends the observed phenomenon of head lice mobility impairment when their environmental temperature deviates significantly from about 32xc2x0 C. Nearly complete mortality occurs from exposure to temperatures of about 46xc2x0 C. for several minutes, and a decrease in mobility is seen when the environmental temperature is reduced below about 30xc2x0 C. Since such elevated or lowered skin temperatures are easily tolerated by humans and most animals, the inventors determined that ectoparasites can be readily removed from the body by simple mechanical means, such as combing with a fine-tooth comb, while the parasites are immobilized. It is generally preferred that the elevated or reduced temperatures be maintained during the combing process, to prevent individual parasites from simply evading the comb if they regain their mobility. The duration of combing will vary, depending upon a subject""s hair density, texture and length, and sometimes amounts to several hours.
Lice egg cases (xe2x80x9cnitsxe2x80x9d) are thought to be attached to hair by means of mucopolysaccharide adhesive substances. Removal of the nits therefore requires a very thorough combing operation, and is not appreciably facilitated by many of the usual pesticide treatments. However, one embodiment of the present invention provides both moisture and heat which tend to degrade the adhesive and facilitate nit removal by combing, as well as probably providing the effects of desiccation and an increased pH in the microenvironment of the nit, both of which are thought to alter the physical and chemical nature of the egg casing itself. Providing lubricious agents in a composition also can facilitate lice and nit removal by combing.
The presence of a desiccating microenvironment about the live lice can cause rapid mortality, as evidenced by physiologic changes in the organisms under microscopic observation. These changes include collapsing of the abdomen. Another property of the self-heating compositions of the present invention which is postulated to affect lice mobility and mortality is an elevation of the microenvironmental pH. The active ingredients for heat generation should create high pH regions on their surfaces, during the hydration reaction; it is likely that ectoparasites do not readily tolerate such conditions and are adversely impacted by the high pH. Of course, it is not possible to measure the actual pH conditions at the particle surface, but this surface pH value is likely to be quite different from the bulk pH of the composition.
Elevated temperatures sufficient for inhibiting the mobility of ectoparasites on the human head can be generated and maintained using various means, such as heated combs and brushes, forced heated air, the application of heated liquids and cap-like devices having a relatively thin chamber over its surface for holding a heated substance, most conveniently hot water or a microwave-susceptible fluid. An appropriate device, for example, can structurally resemble a hot water bottle and be molded from a polymeric substance, in the shape of a shower cap. Such devices will provide adequate temperatures for initially immobilizing the lice, but must be removed for the subsequent combing operation and therefore may not provide a sustained temperature condition. However, if the subject""s hair is sufficiently short, and therefore not requiring a prolonged combing, it is possible to adequately treat an ectoparasite infestation using such devices.
The inventors prefer to generate elevated temperatures on hair-covered body surfaces, using compositions which contain substances that undergo hydration reactions in an exothermic manner. Such compositions have an advantage, in that they can be formulated to generate heat, then remain in place while the mechanical removal of immobilized and killed parasites is effected.
Suitable self-heating compositions for use in the invention generally are non-aqueous in nature, or have only a very small water content, and contain as their active ingredient a substantially anhydrous inorganic component such as a silica, an aluminosilicate, an alkaline earth metal oxide or a combination of such components, which exhibits an exothermic reaction upon contact with water. To maximize heat evolution when the active ingredient contacts water, and to facilitate combing of hair with the composition in place, it is preferred to use particles of the active ingredients having average sizes in the range of about 3 xcexcm to about 6 xcexcm. However, particles having larger or smaller sizes will function adequately in the invention.
Particulate inorganic substances which are useful in the compositions of the invention include materials such as fumed silica, aluminosilicates, aluminum oxide, magnesium oxide and calcium oxide. Typically, the inorganic particulate will be present in a composition in amounts about 1 percent to about 65 percent. The use of aluminosilicates is presently preferred and these include materials commonly known as xe2x80x9czeolites.xe2x80x9d
Zeolites suitable for use in the invention include both the naturally occurring materials and the synthetically produced materials. Zeolites have typically been used as ion-exchange agents, adsorbents for gaseous and liquid chemical substances and as supports for catalysts, such as the catalysts used in petroleum refining. For use in the present invention, the zeolites are xe2x80x9cactivatedxe2x80x9d by removal of their crystalline water content; this is accomplished by heating to relatively high temperatures until the desired water content is obtained, the temperature and duration of heating necessarily being individually determined for each type of zeolite. Presently commercially available activated zeolites that are useful in the invention include, without limitation: MOLSIV(trademark) products sold by UOP LLC of Des Plaines, Ill. USA and identified as Type 3A (potassium aluminosilicate), Type 4A (sodium aluminosilicate) and Type 5A (calcium aluminosilicate). Products being sold by W. R. Grace and Co. of Columbia, Md. U.S.A. under the trademark SYLOSIV are other examples of useful zeolites. Some zeolites are aluminosilicates of mixed alkali metals and/or alkaline earth metals, and these are also well-suited for use in the present invention.
Suitable compositions can be in the forms of a dry powder, a lotion or cream, or a fluid pressurized aerosol. The most simple self-heating compositions frequently will be the dry powders, since the only essential component is the particulate active ingredient; other components, such as dry surfactants, may be added to facilitate combing such as when the composition is applied to moistened hair.
To prepare a preferred fluid form of a self-heating ectoparasite removal composition, including a lotion, cream or aerosol form, the heat-generating inorganic particulate may be suspended in a substantially anhydrous vehicle, such as: a light or heavy mineral oil; a glycol such as polyethylene glycol, propylene glycol or triethylene glycol; glycerol; and the like. Typical concentrations of the vehicle range from about 1 percent to about 60 percent. Selection of the vehicle can affect the heat generation reaction, since a more water-impervious substance such as mineral oil can impede access of water to the particulate solid, and thereby slow the rate of temperature increase and/or the maximum temperature obtained.
It is generally desired to achieve temperatures above about 37xc2x0 C. to maximize efficacy, but to limit the maximum temperature attained by the formulation to about 55xc2x0 C., to avoid discomfort when applied to the body.
Optionally, a suspending agent may be present in the self-heating composition to maintain a more stable dispersion. Useful agents include, without limitation, fumed silica and polyvinylpyrrolidone having molecular weights from about 25,000 to about 100,000, in amounts about 0.1 to about 2 percent.
The compositions may further include other components, such as surfactants, lubricants, texture modifiers, acidifiers, preservatives and other cosmetic-type ingredients used to create desired physical properties.
Useful optional surfactants include, without limitation, sodium lauryl sulfate, sorbitan laurate, mixtures of glyceryl stearate and PEG-100 stearate, methyl gluceth-10, methyl gluceth-40, sorbitan palmitate, polysorbate 20, polysorbate 80, steareth-2 and many others. The surfactants will be present in amounts about 0.1 to about 16 percent, and can create shampoo-type products which are easily removed after the ectoparasite treatment is completed.
The lubricants that can be incorporated are represented by dimethicone, simethicone and other silicone-type materials, and act to lubricate and condition the hair, as well as facilitate passage of a comb through the hair. Useful concentrations, when this component is present, are about 0.1 to about 2 percent.
Optional texture modifiers that may be included are exemplified by stearic acid, cetyl alcohol, PEG-180, polyethylene glycol 1450 and polyethylene glycol 3350, in amounts about 0.1 percent to about 5 percent.
It may be desired to incorporate an acidic ingredient in the composition, since the heat-generating active ingredients tend to produce alkaline suspensions in water. Optional acidifiers that may be used include, without limitation, benzoic acid, citric acid and stearic acid. It is preferred to use anhydrous acidifiers. The acids will generally be present in amounts about 0.1 percent to about 2 percent, as needed to obtain a desired bulk pH condition when the compositions are used.
Products that are intended for application to the skin frequently are protected against microbial proliferation by the inclusion of a preservative component. Suitable preservatives for use in the present compositions include, without limitation, methylparaben, propylparaben and benzethonium chloride. The preservative will typically be included in concentrations about 0.05 to about 0.2 percent.
Included within the scope of the present invention is a kit for treating an ectoparasite infestation, including a suitable container filled with a composition that can be applied to an area of the body to reduce or increase the temperature of the area, together with a mechanical device for removing ectoparasites after they are affected by the composition. For compositions that are in the form of a fluid, such as liquids, lotions and creams, the composition can be contained in a bottle or collapsible tube. Aerosol compositions can be contained in the customary dispensing canisters, fitted with a suitable valve for dispensing the product. Powdered compositions can be contained in one of the customary canisters having a perforated cap for shaking out a desired amount, or in a bottle. Many delousing combs are commercially available, being fabricated from plastic substances or metals, and any of these are suitable for inclusion in the kit. It is preferred that the kit be made suitable for a single use, including sufficient composition for one application.
The invention will be further described with reference to the following examples, which are not intended to limit the scope of the claimed invention in any manner.